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This is an open-access article distributed under the terms of the Creative Commons Attribution License. ; Sirenomelia is a severe congenital malformation of the lower body characterized by the fusion of the legs into a single lower limb. This striking external phenotype consistently associates severe visceral abnormalities, most commonly of the kidneys, intestine, and genitalia that generally make the condition lethal. Although the causes of sirenomelia remain unknown, clinical studies have yielded two major hypotheses: i) a primary defect in the generation of caudal mesoderm, ii) a primary vascular defect that leaves the caudal part of the embryo hypoperfused. Interestingly, Sirenomelia has been shown to have a genetic basis in mice, and although it has been considered a sporadic condition in humans, recently some possible familial cases have been reported. Here, we report that the removal of one or both functional alleles of Shh from the Bmp7-null background leads to a sirenomelia phenotype that faithfully replicates the constellation of external and internal malformations, typical of the human condition. These mutants represent an invaluable model in which we have analyzed the pathogenesis of sirenomelia. We show that the signaling defect predominantly impacts the morphogenesis of the hindgut and the development of the caudal end of the dorsal aortas. The deficient formation of ventral midline structures, including the interlimb mesoderm caudal to the umbilicus, leads to the approximation and merging of the hindlimb fields. Our study provides new insights for the understanding of the mechanisms resulting in caudal body malformations, including sirenomelia. © 2012 Garrido-Allepuz et al. ; The authors should acknowledge the support of the Spanish Ministery of Science and Innovation (BFU2011-24972 to MAR) and I+D+I cooperative projects in Biomedicine and Biotechnology from the Government and University of Cantabria. This work was supported by grant BFU2011-24972 from the Spanish Ministry of Science and Innovation to MAR. ; Peer Reviewed

11 páginas, 4 figuras.-- This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial. ; Sirenomelia, also known as sirenomelia sequence, is a severe malformation of the lower body characterized by fusion of the legs and a variable combination of visceral abnormalities. The causes of this malformation remain unknown, although the discovery that it can have a genetic basis in mice represents an important step towards the understanding of its pathogenesis. Sirenomelia occurs in mice lacking Cyp26a1, an enzyme that degrades retinoic acid (RA), and in mice that develop with reduced bone morphogenetic protein (Bmp) signaling in the caudal embryonic region. The phenotypes of these mutant mice suggest that sirenomelia in humans is associated with an excess of RA signaling and a deficit in Bmp signaling in the caudal body. Clinical studies of sirenomelia have given rise to two main pathogenic hypotheses. The first hypothesis, based on the aberrant abdominal and umbilical vascular pattern of affected individuals, postulates a primary vascular defect that leaves the caudal part of the embryo hypoperfused. The second hypothesis, based on the overall malformation of the caudal body, postulates a primary defect in the generation of the mesoderm. This review gathers experimental and clinical information on sirenomelia together with the necessary background to understand how deviations from normal development of the caudal part of the embryo might lead to this multisystemic malformation. ; Supported by grant BFU2008-00397 (to M.A.R.) and grant BFU2010-19656 (to F.B.) from the Spanish Ministry of Science and Innovation, and by I+D+I cooperative projects in Biomedicine and Biotechnology from the Government and University of Cantabria. ; Peer reviewed

Whether the increased risk for coronavirus disease 2019 (COVID-19) hospitalization and death observed in Down syndrome (DS) are disease specific or also occur in individuals with DS and non-COVID-19 pneumonias is unknown. This retrospective cohort study compared COVID-19 cases in persons with DS hospitalized in Spain reported to the Trisomy 21 Research Society COVID-19 survey (n = 86) with admissions for non-COVID-19 pneumonias from a retrospective clinical database of the Spanish Ministry of Health (n = 2832 patients). In-hospital mortality rates were significantly higher for COVID-19 patients (26.7% vs. 9.4%), especially among individuals over 40 and patients with obesity, dementia, and/or epilepsy. The mean length of stay of deceased patients with COVID-19 was significantly shorter than in those with non-COVID-19 pneumonias. The rate of admission to an ICU in patients with DS and COVID-19 (4.3%) was significantly lower than that reported for the general population with COVID-19. Our findings confirm that acute SARS-CoV-2 infection leads to higher mortality than non-COVID-19 pneumonias in individuals with DS, especially among adults over 40 and those with specific comorbidities. However, differences in access to respiratory support might also account for some of the heightened mortality of individuals with DS with COVID-19. ; The lab of M.D. is supported by the Departament d'Universitats, Recerca i Societat de la Informació de la Generalitat de Catalunya (Grups consolidats 2017 SGR 926, 2017 SGR 138). We also acknowledge the support of the Agencia Estatal de Investigación (PID2019-110755RB-I00/AEI/10.13039/501100011033), the European Union's Horizon 2020 research and innovation programme under grant agreement No 848077, Jerôme Lejeune Foundation (No 2002), NIH (Grant Number: 1R01EB 028159-01), Marató TV3 (#2016/20-30), JPND Heroes project. CRG acknowledges the support of the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa, and the CERCA Programme/Generalitat de Catalunya. The CIBER of Rare Diseases (CIBERER) and CIBER of Physiopathology of Obesity and Nutrition (CIBEROBN) are initiatives of the ISCIII. D.R.A. is partially supported by the Fondo de Investigaciones Sanitarias (FIS grant PI19/00634, European Fund for Regional Development—EFRD) and the Foundation Jérôme Lejeune (grant no. 1777-2018). The Research Programme on Biomedical Informatics (GRIB) is a member of the Spanish National Bioinformatics Institute (INB), funded by ISCIII and EDER (PT17/0009/0014). The DCEXS is a 'Unidad de Excelencia María de Maeztu', funded by the AEI (CEX2018-000782-M). The GRIB is also supported by the Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR), Generalitat de Catalunya (2017 SGR 00519). AH was supported by the HERCULES Center (NIEHS P30ES019776) and by the LuMind IDSC Foundation.

During the COVID-19 pandemic, entire populations were instructed to live in home-confinement to prevent the expansion of the disease. Spain was one of the countries with the strictest conditions, as outdoor physical activity was banned for nearly two months. This study aimed to analyse the changes in physical activity and sedentary behaviours in Spanish university students before and during the confinement by COVID-19 with special focus on gender. We also analysed enjoyment, the tools used and motivation and impediments for doing physical activity. An online questionnaire, which included the International Physical Activity Questionnaire Short Form and certain 'ad hoc' questions, was designed. Students were recruited by distributing an invitation through the administrative channels of 16 universities and a total of 13,754 valid surveys were collected. Overall, university students reduced moderate (-29.5%) and vigorous (-18.3%) physical activity during the confinement and increased sedentary time (+52.7%). However, they spent more time on high intensity interval training (HIIT) (+18.2%) and mind-body activities (e.g., yoga) (+80.0%). Adaptation to the confinement, in terms of physical activity, was handled better by women than by men. These results will help design strategies for each gender to promote physical activity and reduce sedentary behaviour during confinement periods. ; This research was funded by the High Sports Council (Consejo Superior de Deportes, CSD) of the Ministry of Culture and Sports of the Government of Spain, grant number 45/UPB/20. A.E. is a recipient of a grant of the Basque Government (Eusko Jaurlaritza), grant number PRE_2019_1_0373. D.J.-P. is supported by a grant from the Spanish Ministry of Science and Innovation-MINECO, grant number RYC-2014-16938.